Impaired glymphatic clearance is an important cause of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia worldwide. The disease is characterized by the abnormal accumulation of amyloid β (Aβ) protein creating neuritic plaques, hyperphosphorylated tau (p-tau) protein forming intracellular tangles, and neuronal degeneration. Pathological changes related to abnormal Aβ and p-tau accumulation may begin more than fifteen years before the clinical diagnosis of AD is made. The glymphatic system is the brain’s waste clearance pathway that prevents the accumulation of these abnormal proteins and macromolecules. Glymphatic clearance is negatively affected by physiological conditions such as sleep deprivation, and pathological conditions such as traumatic brain injury and hemorrhagic strokes. These physiological and pathological conditions are strong risk factors for AD. In conclusion, impaired glymphatic clearance is an important pathogenetic mechanism for AD.

Keywords

• alzheimer’s disease
• glymphatic system
• amyloid β accumulation
• hyperphosphorylated tau protein
• neurofibrillary tangles
• aquaporin-4